Objective Current carotid artery stenting practice guidelines recommend dual antiplatelets to reduce major adverse cardiovascular events during and after transcarotid revascularization (TCAR). However, some patients are poor candidates for this regimen, due to preexisting need for anticoagulation, allergies, and/or risk of major bleeding. Therefore, this investigation was performed to review outcomes associated with patients undergoing TCAR while on alternative medication regimens to determine safety and efficacy. Methods A retrospective review was performed of a combined database created by the combination of institutional carotid revascularization archives maintained at 2 high-volume TCAR health systems. Patients taking dual antiplatelets were compared to those on nontraditional medications with respect to demographics and perioperative and long-term outcomes. Results Between our 2 member institutions, 729 TCAR procedures, consisting of 549 patients on dual antiplatelets and 180 on alternative treatments, qualified for study inclusion and analyzed. The cohort not taking dual antiplatelets presented with a heavier comorbidity burden by Charlson Comorbidity Index (5.3 ± 2.2 vs 6.1 ± 2.2, P < .01). Additionally, these patients underwent higher risk revascularization procedures, as they had a higher proportion of symptomatic lesions (34.6% vs 43.0%, P = .03). Despite these deviations in baseline characteristics, similar outcomes between groups were observed in the 30-day perioperative period with respect to stroke (2.2% vs 2.8%, P = .58), death (1.3% vs 1.1%, P > .99), and myocardial infarction (.4% vs 0%, P > .99). Similarly, rates of reintervention (1.6% vs 1.1%, P > .99), hematoma formation (2.4% vs 2.2%, P > .99), and stent thrombosis (.5% vs .6%, P > .99) were consistent, regardless of antiplatelet status. At follow-up of 25.4 and 29.1 months, respectively, for the dual antiplatelet and alternative treatment cohorts, no deviations with respect to reintervention, stroke, myocardial infarction, or stent thrombosis were noted. However, there was an increased risk of death (5.4% vs 13.5%, P = .02) in the alternative regimen group. Conclusion In this small series of TCARs, patients not maintained on dual antiplatelets did not experience more perioperative adverse events after TCAR. However, more studies, in larger series, are required to verify and validate these findings.